The research objective is to elucidate the molecular mechanisms by which the essential defense functions of lung macrophages are regulated. Lung macrophages respond to invading microorganisms by moving towards them, and extending pseudopods to engulf them. During ingestion, they secrete proteolytic enzymes, which if uncontrolled, are potentially destructive to lung tissues. Changes in intracellular calcium ion concentration affect the gel-like consistency of the cytoplasm, and thereby control all macrophage defense functions requiring movements of the cytoplasm. Particular attention will be focused on the properties of a newly-discovered heat-labile, 180,000 dalton macrophage protein, which reversibly regulates gel-sol transformation of actin networks in macrophage cytoplasm, depending on the calcium concentration. This protein is to my knowledge, distinct from other calcium-dependent regulatory proteins described so far in muscle or nonmuscle cells, and is likely to be a key control point for many cytological events. The interaction of this protein with components of the actin network will be examined after purification, and possible modifications of contractile proteins will be studied.